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This study determined a 24-month outcome of perampanel (PER) treatment in children and adolescents with drug-resistant epilepsy. The percentage of ≥50% responders was 47.3% at 12 months and 49.0% at 24 months. A 100% reduction in seizures for more than 12 months was observed in 36 patients (12.2%). Discontinuation occurred in 117 patients (39.8%). The most common reason for discontinuation was adverse events (34/117 patients, 11.6%). Baseline seizure frequency was higher in children aged

For the study on the relationships between the seed dispersal of exotic plants and bird population, flora, avifauna, vegetation patches, and the dynamics of seed banks were investigated in and around the exposed floodplains of the large rivers, and the causes of exotic vegetation development were determined with respect to plant life form, bird population characteristics, and landscape using multivariate analysis. The number of dominant exotic plant species observed in exposed areas was higher than that observed in an abandoned field and paddy field undergoing secondary succession. Additionally, the area occupied by exotic vegetation in exposed areas increased with the increase in number of vine plants and small terrestrial birds, whereas the relationship between vine and runner plants was inversely proportional. Therefore, to control exotic plants in exposed floodplains surrounding large rivers, it is necessary to remove vines and shrubs along the waterfront where small resident birds carrying plant seeds live and to maintain and manage runner plant populations. Furthermore, implementing an ecological landscape management strategy, such as afforestation through the planting of trees, may also be effective.

Hulunbuir steppe, one of the four largest grasslands in the world, is suffering progressing desertification due to climate change and anthropogenic disturbance. In this study, the plant species and communities were analyzed with CSR ecological strategies for the succession process that occurred following the introduction of woody plants in the restored site in the damaged steppe, and compared with those in the reference site in an attempt to find the lifeform characteristics of plants in grasslands and implications for success in ecological restoration. According to the results, the introduction of woody plants into the damaged land greatly increased the diversity of plant species and CSR eco-functional diversity as the succession progressed. The types of ecological strategies of the temperate typical steppe (TTS) and woodland steppe (WS) in this region are CSR and S/SR, respectively, which means that plants in the temperate Asian steppe are species basically adapted to natural disturbances such as drying and soil movement. As the restoration time elapsed in the damaged lands (R/CR), the ecological strategies were predicted to change in two ways: R/CR→R/CSR→CSR (TSS) in places where only shrubs were introduced, and S/SR→S/SR (WS) in places where trees and shrubs were introduced simultaneously. The results as such mean that the driving force that causes succession in the restoration of temperate grasslands is determined by the lifeform (trees/shrubs) of the introduced woody plants, and therefore, it is judged that trees or shrubs should be selected and introduced bearing the final target vegetation in mind when planning restoration.

Supplementary Figure 2 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Materials and Methods, Figure Legends 1-7, Table 1 Legend from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Figure 5 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Figure 3 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Table 1 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Figure 1 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Figure 4 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Figure 6 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

Supplementary Figure 7 from Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

The N-acetyltransferase arrest defective 1 (ARD1) is an important regulator of cell growth and differentiation that has emerged recently as a critical molecule in cancer progression. However, the regulation of the enzymatic and biological activities of human ARD1 (hARD1) in cancer is presently poorly understood. Here, we report that hARD1 undergoes autoacetylation and that this modification is essential for its functional activation. Using liquid chromatography-tandem mass spectrometry and site-directed mutational analyses, we identified K136 residue as an autoacetylation target site. K136R mutation abolished the ability of hARD1 to promote cancer cell growth in vitro and tumor xenograft growth in vivo. Mechanistic investigations revealed that hARD1 autoacetylation stimulated cyclin D1 expression through activation of the transcription factors β-catenin and activator protein-1. Our results show that hARD1 autoacetylation is critical for its activation and its ability to stimulate cancer cell proliferation and tumorigenesis. Cancer Res; 70(11); 4422–32. ©2010 AACR.

Purpose: The aim of this study was to identify factors affecting pressure ulcers among cognitive impairment inpatients with long term care facilities. Methods: In this secondary data analysis of the two long-term care facilities, 162 patients with mild or more cognitive impairment were analyzed. Patients with a pressure ulcer of stage 2 or higher that developed after the first day of hospitalization were defined as the pressure ulcer group, while the other patients comprised the non-pressure ulcer group. Demographic characteristics were compared between the two groups. Initially, a univariate analysis was conducted. Subsequently, risk factors were identified through logistic regression analysis using the variables that exhibited statistically significant differences in the univariate analysis. Results: Thirty-three patients had hospital-acquired pressure ulcers. Age (odds ratio [OR]=0.92, 95% confidence interval [CI]=0.87~0.98), albumin levels (OR=0.25, 95% CI=0.08~0.77), Charlson comorbidity index (OR=1.57, 95% CI=1.14~2.18), and Mini-Mental State Examination for Koreans score (OR=0.90, 95% CI=0.81~0.99) were identified as risk factors for pressure ulcer occurrence. Conclusion: Our data analysis supports independent associations between certain clinical characteristics and pressure ulcer occurrence in long-term care facility patients with cognitive impairment. To reduce the risk of pressure ulcers in long-term care facilities, health professionals should implement appropriate prevention measures.

Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus (T2DM). Statin and metformin are commonly used medications in T2DM patients, and some studies showed statin- or metformin-induced neuropathy. AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies. METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used. Patients with T2DM and no complications were divided into statin/metformin/statin + metformin users and non-users. Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems, 10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants. Logistic regression analyses were conducted to examine the associations between statin/metformin/statin + metformin therapies and the incidence of neuropathy. Propensity score (PS) matching was performed on the basis of age, sex and comorbidities. RESULTS Overall, 34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017, respectively. Statin therapy was associated with increased risks of neuropathy in 2016 and 2017 [PS-matched odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; PS-matched OR = 1.17, 95%CI: 1.03-1.33, respectively]. Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017 (PS-matched OR = 0.30, 95%CI: 0.21-0.42; PS-matched OR = 0.44, 95%CI: 0.32-0.60, respectively). Combined statin + metformin therapy was not significantly associated with neuropathy in 2016 or 2017 (PS-matched OR = 0.85, 95%CI: 0.61-1.19; PS-matched OR = 0.95, 95%CI: 0.66-1.38, respectively). CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM, but metformin therapy showed the opposite association.

Objectives To estimate the association between the use of interdental cleaning devices and proximal caries experience. Methods This study used a cross-sectional data from the Sixth Korea National Health and Nutrition Examination Survey (2013-2015). A total of 13 525 adults aged 19-64 years who participated in both the nutrition survey and the health examination survey were included. Data on sociodemographic factors (age and sex), socioeconomic factors (level of education and household income) and personal health practices (frequency of toothbrushing, visits to dental clinic, frequency of snacking and self-rated oral health status), and number of proximal caries were collected. Prevalence ratios (PRs) and 95% confidence intervals (95% CI) were calculated using the multivariable Poisson generalized linear model according to use of dental floss or an interdental brush. The risk of proximal caries for dental floss following the stratification of participants into various subgroups related to oral health was assessed. Results While nonflossers had 1.46 times (PR 1.46, 95% CI: 1.16-1.84) higher risk for proximal caries than flossers, the use of an interdental brush was not associated with proximal caries. In the nonflossers, the association for proximal caries was the strongest in those in their 40s (PR 2.28, 95% CI: 1.29-4.03), followed by those in their 30s (PR 1.85, 95% CI: 1.18-2.90). Although nonflossers with middle-low household income had a 59% higher risk (PR 1.59, 95% CI: 1.24-2.03) for proximal caries than those with high household income, there were no significant differences in household income in flossers. Conclusions The findings of the study suggest that flossing at home along with toothbrushing is one of the easiest ways to prevent proximal caries. Therefore, dental floss should not be excluded from oral healthcare products.

Doxorubicin (DOX), which is widely used in cancer treatment, can induce cardiomyopathy. One of the main mechanisms whereby DOX induces cardiotoxicity involves pyroptosis through the NLR family pyrin domain containing 3 (NLRP3) inflammasome and gasdermin D (GSDMD). Increased NAPDH oxidase (NOX) and oxidative stress trigger pyroptosis. Exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases reactive oxygen species (ROS) production by inactivating NOX. Here, we examined whether 8-OHdG treatment can attenuate DOX-induced pyroptosis in H9c2 cardiomyocytes. Exposure to DOX increased the peroxidative glutathione redox status and NOX1/2/4, toll-like receptor (TLR)2/4, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while an additional 8-OHdG treatment attenuated these effects. Furthermore, DOX induced higher expression of NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a c-terminal caspase recruitment domain (ASC), and pro-caspase-1. Moreover, it increased caspase-1 activity, a marker of pyroptosis, and interleukin (IL)-1β expression. All these effects were attenuated by 8-OHdG treatment. In addition, the expression of the cardiotoxicity markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was increased by DOX, whereas the increase of ANP and BNP induced by DOX treatment was reversed by 8-OHdG. In conclusion, exogenous 8-OHdG attenuated DOX-induced pyroptosis by decreasing the expression of NOX1/2/3, TLR2/4, and NF-κB. Thus, 8-OHdG may attenuate DOX-induced cardiotoxicity through the inhibition of pyroptosis.

BackgroundAge-related changes and different patterns of salivary gland abnormalities according to age may affect the diagnostic performance of unstimulated salivary flow rate (USFR) and salivary gland ultrasound (SGUS) for primary Sjögren's syndrome (pSS). We aimed to evaluate the threshold and diagnostic performance of USFR and whether incorporating SGUS or replacing USFR with SGUS affects the performance of the ACR/EULAR criteria for pSS according to age.Materials and methodsThis medical chart review study included patients with suspected pSS who completed evaluations for pSS. Patients were classified based on age at pSS evaluation: elderly (≥65 years), middle-aged (40–64), and young (< 40). The USFR's optimal thresholds were evaluated using the ROC curve. The diagnostic performances of the USFR and modified ACR/EULAR criteria were compared.ResultsIn total, 239 pSS patients and 92 patients with idiopathic sicca syndrome were included. The cut-off of USFR ≤ 0.1 mL/min was irrelevant to age, demonstrating the best sensitivity (44.3–53.0%) and specificity (74.1–90.9%). SGUS had a significantly better AUC than USFR in the young (p < 0.01) and middle-aged groups (p < 0.01). The middle-aged group demonstrated better diagnostic performance of the ACR/EULAR criteria incorporating SGUS (AUC 0.957) (p < 0.01) and criteria replacing USFR with SGUS (AUC 0.957) (p < 0.001) compared to the original criteria (AUC 0.916). In the young and elderly groups, adding SGUS to the ACR/EULAR criteria or replacing USFR with SGUS did not significantly increase the AUC.ConclusionsThe thresholds of USFR ≤ 0.1 mL/min was optimal, irrespective of age. Using SGUS can improve diagnostic accuracy of ACR/EULAR criteria by supplementing the USFR, especially in middle-aged patients.

Objective It has been known that West syndrome (WS) patients with an unknown etiology have better clinical outcomes than patients with an identified etiology of any kind. However, after the exponential discovery of genes with mutations responsible for developmental and epileptic encephalopathy (DEE), a significant proportion of patients with a previously unknown etiology have been reclassified as having a genetic etiology, requiring reinvestigation of this concept. Therefore, this study investigated clinical outcomes of WS patients with genetic and unknown etiologies. Methods Patients diagnosed with WS without structural or metabolic abnormalities were included in this study. The DEE gene panel, comprising 172 genes, was performed for all patients. All patients were treated using the same treatment protocol for vigabatrin and high-dose prednisolone add-on therapy. Favorable responders were defined as patients who were seizure-free and whose electroencephalogram showed Burden of Amplitudes and Epileptiform Discharges scores of 2 or less. Results Of the 58 patients included in the study, 17 (29.3%) patients had an identified genetic etiology. There was no significant difference in rates of favorable response at 1 and 3 months after treatment, but significantly higher proportions of patients exhibited favorable responses among those with an unknown etiology at long-term follow-up (41.2% vs. 78.0%, p = .006 at 6 months; 29.4% vs. 65.9%, p = .011 at 1 year; 23.5 vs. 65.9%, p = .003 at 2 years). Moreover, the mental, psychomotor, and social age quotients of the patients with an identified genetic etiology were reduced to a significantly greater degree since diagnosis compared with those of the patients with an unknown etiology. Significance WS patients with genetic and unknown etiologies did not initially exhibit significantly different response rates to the vigabatrin and high-dose prednisolone add-on treatment. However, patients with a genetic etiology exhibited significantly higher relapse rates and significantly poorer long-term responses.

This study focused on distinguishing the characteristic ultrasonographic findings of lacrimal glands in primary Sjögren's syndrome (pSS) from those in idiopathic sicca syndrome. We aimed to set up a semi-quantitative scoring system of lacrimal gland ultrasonography (LGUS) for patients with pSS.Fifty-six patients with pSS and 40 patients with idiopathic sicca syndrome were evaluated. Lacrimal glands were examined with ultrasonography using area, major/minor axis length, and five components (presence of intraglandular branch of lacrimal artery, inhomogeneity, hyperechoic bands, hypoechoic areas, and delineation). Except for the area and maximal/minimal length of lacrimal glands, other components were classified as dichotomous variables (present or absent). Using the receiver operating characteristics curve, we inferred the most appropriate combination of LGUS scoring for pSS diagnosis.Patients with pSS had a higher proportion of intraglandular branch of lacrimal artery (70.5% vs. 42.5%, p0.001), inhomogeneity (72.3% vs. 46.3%, p0.001), and hyperechoic bands (56.2% vs. 37.5%, p=0.016) than patients with idiopathic sicca syndrome. LGUS A, which represents the summation of one point assigned for the presence of intraglandular branch of lacrimal artery and one for inhomogeneity, was the most suitable diagnostic criterion (area under curve = 0.724, 95% confidence interval 0.620-0.828). If both sides have a score of 2, it results in a total of 4 points. With a cut-off value of 3 out of 4 points, LGUS A had 60.7% sensitivity, 71.1% specificity, 60.7% positive predictive value, and 72.5% negative predictive value.Semi-quantitative scoring of LGUS was useful when distinguishing patients with pSS from those with idiopathic sicca syndrome. The combination of intraglandular branch of lacrimal artery and inhomogeneity on both sides was most suitable for classifying pSS using LGUS.

To provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015.The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020.We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with NSCLC and 345 (13.0%) were diagnosed with SCLC, respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of EGFR mutation (19% vs 11%) or ALK translocation (38% vs 11%).In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

The incidence of herpes zoster (HZ) in rheumatoid arthritis (RA) patients is greater than that in healthy controls (HC), particularly in RA patients treated with Janus kinase inhibitors (JAKi). Here, we examined the effect of JAKi on CD4+/CD8+ T cells, cytokine production, and regulation of transcriptional factors in RA patients and HC.Peripheral blood mononuclear cells (PBMCs) obtained from RA patients (n=14) and HCs (n=7) were stimulated with varicella zoster virus lysates and exposed to three JAKi inhibitors (ruxolitinib [JAK1/2 inhibitor]; AG490 [JAK2 inhibitor]; and WHI-P154 [JAK3 inhibitor]) in the presence/absence of methotrexate. The CD4+ and CD8+ T cell populations were measured by flow cytometry. Cytokine levels in culture medium were measured by ELISA. Transcription factor expression was examined by RT-qPCR.There was a reduction in the CD4+IFN-γ+, CD4+CD69+IFN-γ+, CD8+IFN-γ+, and CD8+CD69+IFN-γ+ populations, and an increase in the CD4+CD25highFoxp3+ cell population, in PBMCs from RA patients and HCs after exposure to the three JAKi. ELISA revealed a reduction in IFN-γ and granzyme B levels in the presence of JAKi. JAKi reduced expression of mRNA encoding STAT1 and T-bet, but increased that of mRNA encoding STAT5 and Foxp3. Methotrexate plus the highest dose of each JAKi did not affect the Th1, cytotoxic T cell, or Treg populations, the levels of IFN-γ and granzyme B, or expression of transcription factors, significantly.JAKi reduce the Th1/cytotoxic T cell population and increase the Treg population in both RA patients and HC patients.

Epithelial–mesenchymal transition (EMT), a process by which epithelial cells undergo a phenotypic conversion that leads to myofibroblast formation, plays a crucial role in the progression of idiopathic pulmonary fibrosis (IPF). Recently, it was revealed that hypoxia promotes alveolar EMT and that histone deacetylases (HDACs) are abnormally overexpressed in the lung tissues of IPF patients. In this study, we showed that HDAC3 regulated alveolar EMT markers via the AKT pathway during hypoxia and that inhibition of HDAC3 expression by small interfering RNA (siRNA) decreased the migration ability and invasiveness of diseased human lung fibroblasts. Furthermore, we found that HDAC3 enhanced the migratory and invasive properties of fibroblasts by positively affecting the EMT process, which in turn was affected by the increased and decreased levels of microRNA (miR)-224 and Forkhead Box A1 (FOXA1), respectively. Lastly, we found this mechanism to be valid in an in vivo system; HDAC3 siRNA administration inhibited bleomycin-induced pulmonary fibrosis in mice. Thus, it is reasonable to suggest that HDAC3 may accelerate pulmonary fibrosis progression under hypoxic conditions by enhancing EMT in alveolar cells through the regulation of miR-224 and FOXA1. This entire process, we believe, offers a novel therapeutic approach for pulmonary fibrosis.

Purpose We aimed to assess the efficacy and safety of lacosamide in Korean adolescents with Lennox-Gastaut syndrome (LGS), especially in those who concomitantly used other sodium channel blockers (SCBs). Methods We retrospectively reviewed the medical records of adolescents with LGS who initiated lacosamide from ages 16 to 18. The efficacy of lacosamide was evaluated by seizure frequency before and after lacosamide trial. Safety was assessed by lacosamide-related adverse events, consequent dosage titration, and titration effects. We compared the efficacy and safety of lacosamide according to concomitant use of other SCBs. Results In 26 eligible adolescents with LGS, the median age of seizure onset was 2.0 years, and the median age of lacosamide initiation was 17.1 years. At the time of lacosamide initiation, the median number of concomitant antiepileptic drugs was 4, and 23 patients (88%) had tried dietary, surgical, or neuromodulatory therapies. Patients were on lacosamide for a median of 13.5 months with a median maximal dosage of 8.1 kg/mg/day. After lacosamide trial, 11 patients (42%) had an over 50% reduction of seizures. Six patients (23%) had lacosamide-related adverse events. The percentage of patients on concomitant SCBs was higher among non-responders (10 of 15, 67%) than among responders (6 of 11, 55%). Patients taking concomitant SCBs had a higher ratio of adverse effects (5 of 16, 31%) than their counterparts (1 of 10, 10%). Conclusion Lacosamide is an effective and tolerable antiepileptic drug in adolescents with LGS. Concomitant SCB use may lead to less effective treatment and more adverse events.

Citrus peel has been used as a Traditional medicine in Asia to treat coughs, asthma and bronchial disorders. Therefore, the anti-inflammatory effects of 3,5,6,7,3′,4′-hexamethoxyflavone (quercetogetin, QUE) isolated from Citrus unshiu peel were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. The results showed that QUE repressed the production of prostaglandin E2 and nitric oxide by suppressing LPS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase. It also suppressed the production of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α cytokines, and decreased the nuclear translocation of NF-κB by interrupting the phosphorylation of NF-κB inhibitor α in macrophage cells. Based on the finding that QUE inhibited the phosphorylation of ERK protein expression in LPS-induced RAW264.7 cells, it was confirmed that inhibition of inflammatory responses by QUE was mediated via the ERK pathway. Therefore, this study suggests that QUE has strong anti-inflammatory effects, making it a promising compound for use as a therapeutic agent in treating inflammatory lung diseases, such as emphysema.

Background Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3 months of birth and severe interictal epileptiform discharge, including burst suppression. This study assessed the utility of targeted gene panel sequencing in the genetic diagnosis of this disease. Materials and methods Targeted gene panel sequencing was performed in 150 early infantile-onset DEE patients (≤3 months of age), and we extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. Results Of the early infantile-onset DEE patients, 70 were neonatal-onset DEE and the other 80 patients began experiencing seizures from 1 to 3 months after birth. There were 11 different pathogenic or likely pathogenic variants among 34.7% (52/150) of patients with early infantile-onset DEE, in whom KCNQ2, STXBP1, CDKL5, and SCN1A were the major pathogenic variants. Among the neonatal-onset DEE patients, pathological genes were identified in 42.9% (30/70), indicating a significantly higher diagnostic yield than in 27.5% (22/80) of patients who experienced seizure onset 1 to 3 months after birth (p = 0.048). Among the neonatal-onset DEE group, variants in KCNQ2, STXBP1, and CDKL5 were detected at high frequencies, accounting for 66.7% (20/30) of the pathogenic or likely pathogenic variants found in this study. Conclusion Targeted gene panel sequencing demonstrated a high yield of pathogenic variants in the diagnosis of early-onset epileptic encephalopathy, especially in those with neonatal-onset DEE. Early diagnosis of early-onset epileptic encephalopathy may improve the prognosis of patients by earlier selection of appropriate treatment based on pathogenic variant.

A simple and reliable multiplex polymerase chain reaction (PCR) method was developed using sequence-characterized amplified region (SCAR) markers to identify kiwifruit (Actinidia spp.) cultivars. We observed 183 different polymorphic random amplified polymorphic DNA (RAPD) markers using 23 arbitrary primers in 30 kiwifruit cultivars. The number of polymorphic bands per primer varied from five (OPM-15, OPN-05, and OPN-19) to 12 (OPG-01), with an average of eight. Fifty-eight cultivar-specific polymorphic RAPD fragments were converted into 16 SCAR markers after validating their specificity. Among them, 15 SCAR markers retained the dominant behavior of the original RAPD fragment, whereas the KA11_774 SCAR marker showed a co-dominant polymorphism. Based on RAPD and SCAR data sets, cluster analyses were performed with the unweighted pair-group method of arithmetic averages. The mean genetic similarities were estimated as 0.703 and 0.677 using the RAPD and SCAR markers, respectively. Thirty kiwifruit cultivars were divided into three clusters for RAPD analysis and into two clusters for SCAR analysis, based on a similarity value of 0.67. Overall, the kiwifruit cultivars with a similar breeding background tended to cluster together. Therefore, RAPD and SCAR markers could be successfully applied to assay genetic relationships for kiwifruit cultivar identification. Cluster analysis of combined RAPD and SCAR markers showed very similar results when compared to the RAPD analysis in dendrogram form. The kiwifruit cultivars tested in this study could be identified using only 10 different SCAR markers (KB08_182, KK08_287, KG19_295, KN15_316, KG01_411, KF07_433, KG09_468, KG09_477, KL01_764, and KA11_774). Furthermore, we optimized SCAR markers for simultaneous identification of the 30 kiwifruit cultivars by multiplex PCR, using two sets of five SCAR primer pairs. The developed SCAR markers and multiplex PCR approach facilitate efficient identification of kiwifruit cultivars.

Approximately 50 million people have epilepsy worldwide. Prognosis may vary among patients depending on their seizure semiology, age of onset, seizure onset location, and features of electroencephalogram (EEG). Several researchers have focused on EEG patterns and demonstrated that EEG patterns of individuals with epilepsy can be used to predict prognosis and treatment responses. However, accurate EEG analysis requires an experienced epileptologist with several years of training, who are often unavailable in small or medium sized hospitals. In this paper, a novel machine learning (ML) model that accurately distinguishes Benign Epilepsy with Centrotemporal Spikes (BECTS) from Temporal Lobe Epilepsy (TLE) is proposed. BECTS and TLE show different seizure types and age of onset, but differential diagnosis can be challenging due to the similar location and patterns of the EEG spikes. The proposed hybrid machine learning (HML) model processes the diagnosis in the order of (1) creating feature matrices using statistical indexes after signal decomposition, (2) processing feature selection using Support Vector Machine (SVM) technology, and (3) classifying the results through ensemble learning based on decision trees. Simulation was performed using real patient data of 112 BECTS and 112 TLE EEG signals, where training was performed using 80% of the data and 20% of the data was used in the performance analysis comparison with the actual labeled data based on the diagnosis of medical doctors. The performance of the hybrid classification model is compared with other representative ML algorithms, which include logistic regression, KNN, SVM, and ensemble learning based decision tree. The model proposed in this paper shows an accuracy performance exceeding 99%, which is higher than the performance obtainable from the other ML classification models. The purpose of this study is to introduce a novel EEG diagnostic system that shows maximum efficiency to support clinical real-time diagnosis that can accurately distinguish epilepsy types. Future research will focus on expanding this ML model to categorize other types of epilepsies beyond BECTS and TLE and implement the HML diagnostic blockchain database into the hospital system.

Coupling solar cells with energy storage devices promises to overcome issues associated with intermittency and longevity of the individual systems. Despite such significance of the coupled power sources, most previous approaches have involved bulky configurations with inactive components, eventually hindering their application as portable power sources. Furthermore, to enable practical/versatile applications of the coupled power sources, their operating voltages should be widened and customized for a specific purpose. Here, we demonstrate voltage-tunable portable power supplies based on tailored integration of interdigitated-back-contact-structured crystalline-silicon photovoltaics (cSiPV) and printed bipolar quasi-solid-state lithium-ion batteries (bQSSBs). The maximum power voltages of the cSiPVs and end-of-charge voltages of the bQSSBs are respectively varied and mutually matched to widen the operating voltage window (2.7–13.5 V) of cSiPV–bQSSB. The resulting cSiPV–bQSSB achieves high overall efficiency (10.2%) and stable photo-rechargeable cyclability. Moreover, cSiPV–bQSSB featuring a customized operating voltage is seamlessly unitized with various electronic devices and exhibits sustainable long-time operation under variable weather conditions.

Founded in 1969, the National Museum of Modern and Contemporary Art, Korea (MMCA) was transformed into an executive agency in 2006 and became the subject of performance management. The purpose of this study is to understand the historical and contextual background of performance management reform in South Korea and its application to MMCA, and also to analyze the mechanism of performance evaluation and its consequence on the management of a national art museum. For the analysis, MMCA’s annual reports, performance evaluation records, public announcements and proposed schemes of previous directors, and other related news, articles and available information from 2007 to 2017 were collated, and the changes in performance evaluation measures (by index weight) were chronologically compared, reorganized and interpreted in regard to the internal situation of the museum and its directorship. The main finding was that overtime performance index weight in the evaluation result shows a growing emphasis on the directorship term related, urgent and more quantifiable performance goals, which are in support of the further reform of MMCA as a corporate entity. Also, the changes in evaluation composition signal a trend that the most prioritized task of each directorship term differed, and this ultimately caused less quantifiable performances, such as art collection and research related tasks, to weaken in emphasis as part of the performance. In conclusion, the performance management of MMCA from 2007 to 2017 had a beneficial side in promoting the result-based performance specifically and had functioned as a governing tool that effectively engaged and pressured certain urgent tasks to completion, but it also had a weakness in keeping the long term stability of directorship and provoking the continuous development of all parts of art related core competency. The consequence of performance management can be argued as limiting the understanding/evaluation of directorship competency to the achievements that are distinguished and identifiable, therefore the result is difficult to argue for its justification and sufficiency as a representable score of the art museum performance.

Epithelial–mesenchymal transition (EMT) has been implicated in cancer progression, invasion, and metastasis. We aimed to evaluate the correlations between clinicopathological characteristics and EMT markers in patients with hepatocellular carcinoma (HCC) who underwent surgical resection and to identify the key regulator in EMT process. Fresh-frozen HCC tissues and adjacent nontumor liver tissues from 30 patients who underwent surgical resection were provided by the Gachon University Gil Medical Center Bio Bank. Human HCC cell lines, Hep3B, SNU449, and Huh7 cells were transfected with Rac1 siRNA and exposed to hypoxic conditions. The combined EMT markers expression (down-expression of E-cadherin and overexpression of p21-activated kinases 1 (PAK1)/Snail) by Western blot in HCC tissues when compared to adjacent nontumor liver tissues was significantly associated with macrovascular invasion (p = 0.021), microvascular invasion (p = 0.001), large tumor size (p = 0.021), and advanced tumor stage (p = 0.015). Patients with combined EMT markers expression showed early recurrence and poor overall survival. In vitro studies showed that Rac1 knockdown decreased the expression of EMT markers including PAK1 and Snail in hypoxia-induced Hep3B cells and suppressed the migration and invasion of hypoxia-induced HCC cells. Rac1 may be a potential therapeutic target for inhibition of EMT process through the inhibition of PAK1 and Snail in HCC.